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Enzymatic Reaction Kinetics
Published in Debabrata Das, Debayan Das, Biochemical Engineering, 2019
A competitive inhibitor has strong structural resemblance to the substrate, and the substrate and the inhibitor compete for the same active site of the enzyme. The formation of an enzyme–inhibitor complex reduces the available surface area of the enzyme for interaction with the substrate and that largely decreases the reaction rate. A competitive inhibitor normally combines reversibly with an enzyme. Therefore, the effect of the inhibitor can be minimized by increasing the substrate concentration, unless the substrate concentration is greater than the concentration at which the substrate itself inhibits the reaction. The mechanism of competitive inhibition can be expressed as follows: () E+S↔k2k1ES () E+I↔k4k3EI () ES→k5E+P
Pharmaceuticals: Some General Aspects
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Enzyme inhibitor drugs are used to treat chronic diseases and disorders such as cardiovascular diseases (angina and myocardial infarction, heart failure, hypertensive heart and rheumatic heart disease, etc.), gastrointestinal diseases, Diabetes Type 2, pain, fever, inflammation, neurodegenerative diseases such as Parkinson’s and Alzheimer’s, asthma and COPD, psoriasis and psoriatic arthritis, different infectious diseases (trypanosomiasis, leishmaniasis, tuberculosis, malaria, acquired immunodeficiency syndrome, etc.), a variety of different types of cancers (see below), some of the rare lysosomal storage diseases, life style related conditions (erectile dysfunction, benign prostatic hyperplasia, alopecia) and many others.
Biodegradation of Phenol
Published in Donald L. Wise, Debra J. Trantolo, Remediation of Hazardous Waste Contaminated Soils, 2018
C. Vipulanandan, S. Wang, S. Krishnan
The inhibition of bacterial growth is often due to the inhibition of enzyme systems. An enzyme inhibitor reduces the rate of an enzymatically catalyzed reaction by binding either with the free enzyme and/or with the enzyme-substrate complex. Three types of models are frequently used to explain cell growth inhibition: competitive, noncompetitive, and uncompetitive. Competitive inhibition occurs when a substrate competes with another substrate for a site on either the cell or the enzyme. Noncompetitive inhibition occurs when the inhibitor can combine with both the free cell or enzyme and the cell/enzyme–substrate complex. An uncompetitive inhibitor binds with the cell/enzyme-substrate complex, which cannot undergo further reaction to yield product. Uncompetitive inhibition is believed to be the most frequently responsible mechanism for cell growth inhibition.
Experimental and computational analysis of N-methylcytisine alkaloid in solution and prediction of biological activity by docking calculations
Published in Molecular Physics, 2022
Fanny C. Alvarez Escalada, Elida Romano, Silvia Antonia Brandán, Ana E. Ledesma
The top poses of molecular docking for NMC in the biological receptors were considered as the initial models for ONIOM calculation. All residues that interacted with ligand in the binding site were considered. To compute the binding energy an NMC receptor two-layer ONIOM calculation [30] in the gaussian09 program was performed. In this work, the high-level layer includes the NMC atoms and the low-level layer includes all residues’ atoms in the binding site to evaluate the possible NMC–protein [31] interactions adequately. The B3LYP-6311++G** method was employed to ligand and PM6 semi-empirical was used for the low layer, thus the ONIOM (B3LYP-6311++G**:PM6) level was used to study the complexes. To estimate the donor–acceptor interactions in the active site of each of the enzyme-inhibitor complexes, the natural bond orbital (NBO) population analysis was performed at that level of theory using the NBO 5.1 program.
Current developments in chemistry, coordination, structure and biological aspects of 1-(acyl/aroyl)-3- (substituted)thioureas: advances Continue …
Published in Journal of Sulfur Chemistry, 2019
Aamer Saeed, Muhammad Naeem Mustafa, Muhammad Zain-ul-Abideen, Ghulam Shabir, Mauricio F. Erben, Ulrich Flörke
1-Palmitoyl-3-(substituted phenyl)thioureas 64a-j were demonstrated to have significant jack bean urease inhibitory activities. Particularly, 1-(4-chlorophenyl)-3-palmitoylthiourea 64a bearing 4-chloro substituted phenyl ring was the best inhibitor (IC50 = 0.0170 μM) compared to the standard thiourea (IC50 = 4.720 μM). Lineweaver–Burk plots revealed that compound 64a is a non-competitive enzyme inhibitor. Docking studies against jack bean urease enzyme were performed to determine the binding affinity of the compounds. Analogues 64c and 64e showed the highest binding affinity with the active binding site of urease. The chemo-informatics properties revealed that all target compounds possess drug-like behavior and therefore, such compounds might be further manipulated in medicinal chemistry [131] (Figure 38).
Exploration of ligand-induced protein conformational alteration, aggregate formation, and its inhibition: A biophysical insight
Published in Preparative Biochemistry and Biotechnology, 2018
Saima Nusrat, Rizwan Hasan Khan
Isothermal titration calorimetry quantifies the global heat change taking place in protein during complex formation with ligands (at a constant temperature). ITC is performed when ligand is titrated into a solution containing protein, thereby generating or absorbing heat and gives the result in terms of thermodynamic parameters. Almost all chemical and biochemical processes involve heat change virtually, thus ITC could be recommended for several applications like protein–peptide, protein–protein, protein–ligand, enzyme–inhibitor or enzyme–substrate, binding studies of antibody–antigen, DNA–protein interactions as well as enzyme kinetics. Many different techniques are used to study protein–ligand interaction, which are listed in Table 2.